In the US, pancreatic cancer is the fourth leading cause of cancer-related death and is responsible for over 37,000 annual deaths. Prognosis is poor because most pancreatic cancers are diagnosed late in the progression of the disease, with only 5% of patients alive 5 years after initial diagnosis. Understanding the etiology of pancreatic cancer is critical to implement steps towards prevention and may concurrently provide insights on how to detect this highly fatal disease. Unfortunately, the causes of pancreatic cancer have been largely elusive and other than eliminating cigarette smoking and reducing obesity, opportunities for prevention are absent. Chronic pancreatitis and inflammation are thought to play a critical role in pancreatic carcinogenesis. Epidemiologic studies suggest that Helicobacter pylori infection and periodontal disease increase the risk of pancreatic cancer. We recently reported a 2-fold increase in risk of pancreatic cancer among individuals with high levels of antibodies to a pathogenic strain of Porphyromonas gingivalis (OR = 2.38, 95% CI =1.16-4.90, comparing >200 ng/ml vs. <200ng/ml). These findings underscore the need to perform a tissue based analysis to fully unveil the multifactorial microbial nature of pancreatic cancer. Thus, we propose to examine the human microbiota in pancreatic cancer patients, building from our expertise with the Human Microbiome Project. Our pilot study on pancreatic cancer tissue (fresh and paraffin-embedded) shows high levels of oral bacteria in all tissues tested thus far. For this proposal, we propose to (1) measure microbiota in patients with pancreatic cancer, and in subjects who did not have cancer using a combination of state-of-the-art molecular techniques; (2) examine possible routes of bacteria dissemination from the mouth to the pancreas. While this project will not be able to address causality directly, it will provide valuable data to complement ongoing and future epidemiologic studies examining the role of bacteria in pancreatic cancer. This project is timely and highly relevant to the goals of the NIH Roadmap and the NIH Human Microbiome Project (HMP). Findings from this project will provide key data on the role of bacteria in pancreatic cancer and may provide new opportunities for prevention of this rapidly fatal disease, or for the development of early-stage detection biomarkers.